Analysis of clinical features, genomic landscapes and survival outcomes in HER2-low breast cancer.
J Transl Med
; 21(1): 360, 2023 06 01.
Article
em En
| MEDLINE
| ID: mdl-37264417
ABSTRACT
BACKGROUND:
Novel human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugates prompt the identification of the HER2-low subtype. However, the biological significance of HER2-low expression in breast cancer is unclear.METHODS:
Clinical and genomic data of 579 metastatic breast cancer patients were reviewed from our next-generation sequencing (NGS) database and genomic analysis of early breast cancer patients from TCGA was also analyzed.FINDINGS:
First, the clinicopathological characteristics of HER2-low patients were profoundly influenced by HR status and no difference of prognosis was observed between HER2-low and HER2-zero patients when paired by HR status, but notably HER2-low patients showed similar metastatic patterns to HER2-positive patients in the HR-positive (HR+ ) subgroup, with more brain and initial lung metastases and more cases of de novo stage IV breast cancer than HER2-zero patients. Second, among patients with primary HER2-low or HER2-zero tumors, the discordance of HER2 status between primary and metastatic tumors was significant, with 48.4% of patients with HER2-zero primary tumors exhibiting HER2-low phenotype in metastatic tumors in the HR+ subgroup. Third, within HR+ and HR-negative subtypes, HER2-low and HER2-zero tumors showed no substantial differences in mutation alterations and copy number variations. Forth, germline BRCA2 mutations were observed only in HER2-low patients in our NGS database, especially in HR+ HER2-low tumors. Finally, three molecular subtypes based on genomic alterations in HER2-low breast cancer were identified, which provided novel insights into heterogeneity in HER2-low breast cancer.CONCLUSIONS:
After correcting for HR expression, only marginal differences in clinical and molecular phenotypes were determined between HER2-low and HER2-zero breast cancer. Therefore, HER2-low breast cancer is insufficient to be defined as a distinct molecular entity, but rather a heterogenous disease.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article